Mechanisms of post-flight orthostatic intolerance

Post-flight orthostatic intolerance is a dramatic physiological consequence of human adaptation to microgravity made inappropriate by a sudden return to 1-G. The immediate mechanism is almost always a failure to maintain adequate tissue perfusion, specifically perfusion of the central nervous system, but vestibular dysfunction may occasionally be the primary cause. Orthostatic intolerance is present in a wide range of clinical disorders of the nervous and cardiovascular systems. The intolerance that is produced by spaceflight and 1-G analogs (bed rest, head-down tilt at a moderate angle, water immersion) is different from its clinical counterparts by being only transiently present in subjects who otherwise have normal cardiovascular and regulatory systems. However, the same set of basic pathophysiological elements should be considered in the analysis of any form of orthostatic intolerance.     

Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures

The development of orthostatic hypotension and instability immediately after return from spaceflight has been a significant operational problem to astronauts for more than four decades. Significant reductions in stroke volume and peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with reduced circulating blood volume, although cardiac atrophy might also contribute. Space flight and ground based experiments have demonstrated that an inability to provide adequate peripheral vasoconstriction in astronauts that become presyncopal may be associated with several mechanisms including reduced sympathetic nerve activity, arterial smooth muscle atrophy and/or hyporeactivity, hypersensitivity of beta-adrenergic receptors, etc. In addition, an inability to provide adequate tachycardia in presyncopal subjects may be associated with reduced carotid-cardiac baroreflex sensitivity. Based on the current knowledge and understanding of cardiovascular mechanisms that are altered during exposure to microgravity, a major focus of future research should be directed to the systematic evaluation of potential countermeasures that specifically target and restore the function of these mechanisms. Based on a preliminary systematic evaluation presented in this review, acute physical exercise designed to elicit maximal effort, G-suit inflation, artificial gravity, and specific pharmacological interventions, alone or in combination, have shown promise as successful countermeasures that provide protection against post-flight orthostatic intolerance.     

Vascular perturbations in the chronic orthostatic intolerance of the postural orthostatic tachycardia syndrome.

Chronic orthostatic intolerance is often related to the postural orthostatic tachycardia syndrome (POTS). POTS is characterized by upright tachycardia. Understanding of its pathophysiology remains incomplete, but edema and acrocyanosis of the lower extremities occur frequently. To determine how arterial and venous vascular properties account for these findings, we compared 13 patients aged 13-18 yr with 10 normal controls. Heart rate and blood pressure were continuously recorded, and strain-gauge plethysmography was used to measure forearm and calf blood flow, venous compliance, and microvascular filtration while the subject was supine and to measure calf blood flow and calf size change during head-up tilt. Resting venous pressure was higher in POTS compared with control (16 vs. 10 mmHg), which gave the appearance of decreased compliance in these patients. The threshold for edema formation decreased in POTS patients compared with controls (8.3 vs. 16.3 mmHg). With tilt, early calf blood flow increased in POTS patients (from 3.4 +/- 0.9 to 12.6 +/- 2.3 ml. 100 ml(-1). min(-1)) but did not increase in controls. Calf volume increased twice as much in POTS patients compared with controls over a shorter time of orthostasis. The data suggest that resting venous pressure is higher and the threshold for edema is lower in POTS patients compared with controls. Such findings make the POTS patients particularly vulnerable for edema fluid collection. This may signify a redistribution of blood to the lower extremities even while supine, accounting for tachycardia through vagal withdrawal.     

Midodrine prevents orthostatic intolerance associated with simulated spaceflight.

Many astronauts after being weightless in space become hypotensive and presyncopal when they assume an upright position. This phenomenon, known as orthostatic intolerance, may interfere with astronaut function during reentry and after spaceflight and may limit the ability of an astronaut to exit a landed spacecraft unaided during an emergency. Orthostatic intolerance is more pronounced after long-term spaceflight and is a major concern with respect to the extended flights expected aboard the International Space Station and for interplanetary exploration class missions, such as a human mission to Mars. Fully effective countermeasures to this problem have not yet been developed. To test the hypothesis that alpha-adrenergic stimulation might provide an effective countermeasure, we conducted a 16-day head-down-tilt bed-rest study (an analog of weightlessness) using normal human volunteers and administered the alpha(1)-agonist drug midodrine at the end of the bed-rest period. Midodrine was found to significantly ameliorate excessive decreases in blood pressure and presyncope during a provocative tilt test. We conclude that midodrine may be an effective countermeasure for the prevention of orthostatic intolerance following spaceflight.     

Skin surface cooling improves orthostatic tolerance following prolonged head-down bed rest

Prolonged exposure to microgravity, as well as its ground-based analog, head-down bed rest (HDBR), reduces orthostatic tolerance in humans. While skin surface cooling improves orthostatic tolerance, it remains unknown whether this could be an effective countermeasure to preserve orthostatic tolerance following HDBR. We therefore tested the hypothesis that skin surface cooling improves orthostatic tolerance after prolonged HDBR. Eight subjects (six men and two women) participated in the investigation. Orthostatic tolerance was determined using a progressive lower-body negative pressure (LBNP) tolerance test before HDBR during normothermic conditions and on day 16 or day 18 of 6° HDBR during normothermic and skin surface cooling conditions (randomized order post-HDBR). The thermal conditions were achieved by perfusing water (normothermia ～34°C and skin surface cooling ～12-15°C) through a tube-lined suit worn by each subject. Tolerance tests were performed after ～30 min of the respective thermal stimulus. A cumulative stress index (CSI; mmHg LBNP·min) was determined for each LBNP protocol by summing the product of the applied negative pressure and the duration of LBNP at each stage. HDBR reduced normothermic orthostatic tolerance as indexed by a reduction in the CSI from 1,037 ± 96 mmHg·min to 574 ± 63 mmHg·min (P < 0.05). After HDBR, skin surface cooling increased orthostatic tolerance (797 ± 77 mmHg·min) compared with normothermia (P < 0.05). While the reduction in orthostatic tolerance following prolonged HDBR was not completely reversed by acute skin surface cooling, the identified improvements may serve as an important and effective countermeasure for individuals exposed to microgravity, as well as immobilized and bed-stricken individuals.     

Human muscle function following prolonged eccentric exercise

4 subjects performed repeated eccentric contractions with leg extensors during prolonged downhill walking (-25% gradient) at 6.44 km.h-1 until collapse due to muscle weakness (range of exercise duration 29 to 40 min). During the exercise oxygen uptake rose progressively from approximately 45% of the previously determined VO2max at 10 min to approximately 65% at the end of the exercise. Following the exercise there was an immediate, significant, and sustained reduction in maximal voluntary isometric contraction, and short term (anaerobic) power output measured concentrically on an isokinetic ergometer. These reductions in muscle function persisted for 96 hours post exercise, and were reflected by significant reductions in the tension generated at low frequency (20 Hz) relative to higher frequency (50 Hz) percutaneous stimulation of the quadriceps. All four subjects showed an increase in plasma levels of creatine kinase post eccentric exercise. Performing concentric contractions by walking uphill for one hour at a significantly greater metabolic cost failed to induce comparable reductions in muscle function. These results provide evidence for the consequences of prolonged eccentric work upon dynamic function which complements earlier reports of structural, enzymatic, and static function changes.     

Mechanisms contributing to knee extensor strength loss after prolonged running exercise.

The aim of this study was to identify the mechanisms that contribute to the decline in knee extensor (KE) muscles strength after a prolonged running exercise. During the 2 days preceding a 30-km running race [duration 188.7 +/- 27.0 (SD) min] and immediately after the race, maximal percutaneous electrical stimulations (single twitch, 0.5-s tetanus at 20 and 80 Hz) were applied to the femoral nerve of 12 trained runners. Superimposed twitches were also delivered during isometric maximal voluntary contraction (MVC) to determine the level of voluntary activation (%VA). The vastus lateralis electromyogram was recorded. KE MVC decreased from pre- to postexercise (from 188.1 +/- 25.2 to 142.7 +/- 29.7 N x m; P < 0.001) as did %VA (from 98.8 +/- 1.8 to 91.3 +/- 10.7%; P < 0.05). The changes from pre- to postexercise in these two variables were highly correlated (R = 0.88; P < 0.001). The modifications in the mechanical response after the 80-Hz stimulation and M-wave peak-to-peak amplitude were also significant (P < 0.001 and P < 0.05, respectively). It can be concluded that 1) central fatigue, neuromuscular propagation, and muscular factors are involved in the 23.5 +/- 14.9% reduction in MVC after a prolonged running bout at racing pace and 2) runners with the greatest KE strength loss experience large activation deficit.     

Autonomic dysfunction syndromes associated with orthostatic intolerance

In recent years increased interest has focused on the nature and pathophysiology of orthostatic intolerance and syndromes associated with autonomic disorders. Understanding the pathophysiology underlying these syndromes has led to the recognition of several distinct clinical entities with overlapping features and the associated need to reclassify many of the previously unrecognized syndromes. Among the clinical manifestations, syncope and near syncope are frequently associated with orthostatic intolerance. In addition, however, a wide spectrum of symptoms have been described ranging from chronic fatigue to recurrent neurally mediated vasodepressor reactions. The present review focuses on the pathophysiology and classification of syndromes of autonomic dysfunction associated with orthostatic intolerance. Primary and secondary causes of dysautonomia as well as therapeutic approach to these frequently unrecognized syndromes is presented.     

Cardiac function following prolonged exercise: influence of age

This study sought to determine the influence of age on the left ventricular (LV) response to prolonged exercise (PE; 150 min). LV systolic and diastolic performance was assessed using echocardiography (ECHO) before (pre) and 60 min following (post) exercise performed at 80% maximal aerobic power in young (28 ± 4.5 years; n = 18; mean ± SD) and middle-aged (52 ± 3.9 years; n = 18) participants. LV performance was assessed using two-dimensional ECHO, including speckle-tracking imaging, to determine LV strain (LV S) and LV S rate (LV SR), in addition to Doppler measures of diastolic function. We observed a postexercise elevation in LV S (young: -19.5 ± 2.1% vs. -21.6 ± 2.1%; middle-aged: -19.9 ± 2.3% vs. -20.8 ± 2.1%; P < 0.05) and LV SR (young: -1.19 ± 0.1 vs. -1.37 ± 0.2; middle-aged: -1.20 ± 0.2 vs. -1.38 ± 0.2; P < 0.05) during recovery in both groups. Diastolic function was reduced during recovery, including the LV SR ratio of early-to-late atrial diastolic filling (SR(e/a)), in young (2.35 ± 0.7 vs. 1.89 ± 0.5; P < 0.01) and middle-aged (1.51 ± 0.5 vs. 1.05 ± 0.2; P < 0.01) participants, as were conventional indices including the E/A ratio. Dobutamine stress ECHO revealed a postexercise depression in LV S in response to increasing dobutamine dose, which was similar in both young (pre-exercise dobutamine 0 vs. 20 μg·kg(-1)·min(-1): -19.5 ± 2.1 vs. -27.2 ± 2.2%; postexercise dobutamine 0 vs. 20 μg·kg(-1)·min(-1): -21.6 ± 2.1 vs. -23.7 ± 2.2%; P < 0.05) and middle-aged participants (pre: -19.9 ± 2.3 vs. -25.3 ± 2.7%; post: -20.8 ± 2.1 vs. -23.5 ± 2.7; P < 0.05). This was despite higher noradrenaline concentrations immediately postexercise in the middle-aged participants compared with young (4.26 ± 2.7 nmol/L vs. 3.00 ± 1.4 nmol/L; P = 0.12). These data indicate that LV dysfunction is observed following PE and that advancing age does not increase the magnitude of this response.     

Substrate usage during prolonged exercise following a preexercise meal

The effect of a high-carbohydrate meal 4 h before 105 min of exercise at 70% of maximal O2 uptake was determined in seven endurance-trained cyclists and compared with exercise following a 16-h fast. The preexercise meal produced a transient elevation of plasma insulin and blood glucose, which returned to fasting basal levels prior to the initiation of exercise. The meal also resulted in a 42% elevation (P less than 0.05) of glycogen within the vastus lateralis at the beginning of exercise. The 1st h of exercise when subjects were fed was characterized by a 13-25% decline (P less than 0.05) in blood glucose concentration, a suppression of the normal increase in plasma free fatty acids and blood glycerol, and a 45% (P less than 0.05) greater rate of carbohydrate oxidation compared with exercise when subjects were fasted. After 105 min of exercise, there were no significant differences when subjects were fed or fasted regarding blood glucose levels, rate of carbohydrate oxidation, or muscle glycogen concentration. The greater muscle glycogen utilization (97 +/- 18 vs. 64 +/- 8 mmol glucosyl units X kg-1; P less than 0.05) and carbohydrate oxidation when subjects were fed appeared to be derived from the glycogen synthesized following the meal. These results indicate that preexercise feedings alter substrate availability despite a return of plasma insulin to fasting levels prior to exercise and that these effects persist until the 2nd h of exercise.     

Hemodynamics of orthostatic intolerance: implications for gender differences

Women have a greater incidence of orthostatic intolerance than men. We hypothesized that this difference is related to hemodynamic effects on regulation of cardiac filling rather than to reduced responsiveness of vascular resistance during orthostatic stress. We constructed Frank-Starling curves from pulmonary capillary wedge pressure (PCWP), stroke volume (SV), and stroke index (SI) during lower body negative pressure (LBNP) and saline infusion in 10 healthy young women and 13 men. Orthostatic tolerance was determined by progressive LBNP to presyncope. LBNP tolerance was significantly lower in women than in men (626.8 +/- 55.0 vs. 927.7 +/- 53.0 mmHg x min, P < 0.01). Women had steeper maximal slopes of Starling curves than men whether expressed as SV (12.5 +/- 2.0 vs. 7.1 +/- 1.5 ml/mmHg, P < 0.05) or normalized as SI (6.31 +/- 0.8 vs. 4.29 +/- 0.6 ml.m-2.mmHg-1, P < 0.05). During progressive LBNP, PCWP dropped quickly at low levels, and reached a plateau at high levels of LBNP near presyncope in all subjects. SV was 35% and SI was 29% lower in women at presyncope (both P < 0.05). Coincident with the smaller SV, women had higher heart rates but similar mean arterial pressures compared with men at presyncope. Vascular resistance and plasma norepinephrine concentration were similar between genders. We conclude that lower orthostatic tolerance in women is associated with decreased cardiac filling rather than reduced responsiveness of vascular resistance during orthostatic challenges. Thus cardiac mechanics and Frank-Starling relationship may be important mechanisms underlying the gender difference in orthostatic tolerance.     

Microgravity-induced changes in aortic stiffness and their role in orthostatic intolerance.

Microgravity (microG)-induced orthostatic intolerance (OI) in astronauts is characterized by a marked decrease in cardiac output (CO) in response to an orthostatic stress. Since CO is highly dependent on venous return, alterations in the resistance to venous return (RVR) may be important in contributing to OI. The RVR is directly dependent on arterial compliance (C(a)), where aortic compliance (C(ao)) contributes up to 60% of C(a). We tested the hypothesis that microG-induced changes in C(a) may represent a protective mechanism against OI. A retrospective analysis on hemodynamic data collected from astronauts after 5- to 18-day spaceflight missions revealed that orthostatically tolerant (OT) astronauts showed a significant decrease in C(a) after spaceflight, while OI astronauts showed a slight increase in C(a). A ground-based animal model simulating microG, hindlimb-unweighted rats, was used to explore this phenomenon. Two independent assessments of C(ao), in vivo pulse wave velocity (PWV) of the thoracic aorta and in vitro pressure-diameter squared relationship (PDSR) measurements of the excised thoracic aorta, were determined. PWV showed a significant increase in aortic stiffness compared with control, despite unchanged blood pressures. This increase in aortic stiffness was confirmed by the PDSR analysis. Thus both actual microG in humans and simulated microG in rats induces changes in C(ao). The difference in C(a) in OT and OI astronaut suggests that the microG-induced decrease in C(a) is a protective adaptation to spaceflight that reduces the RVR and allows for the maintenance of adequate CO in response to an orthostatic stress.     

Upregulation of NOS by simulated microgravity, potential cause of orthostatic intolerance.

Prolonged exposure to microgravity during spaceflight or extended bed rest results in cardiovascular deconditioning, marked by orthostatic intolerance and hyporesponsiveness to vasopressors. Earlier studies primarily explored fluid and electrolyte balance and baroreceptor and vasopressor systems in search of a possible mechanism. Given the potent vasodilatory and natriuretic actions of nitric oxide (NO), we hypothesized that cardiovascular adaptation to microgravity may involve upregulation of the NO system. Male Wistar rats were randomly assigned to a control group or a group subjected to simulated microgravity by hindlimb unloading (HU) for 20 days. Tissues were harvested after death for determination of total nitrate and nitrite (NOx) as well as endothelial (e), inducible (i), and neuronal (n) NO synthase (NOS) proteins by Western blot. Separate subgroups were used to test blood pressure response to norepinephrine and the iNOS inhibitor aminoguanidine. Compared with controls, the HU group showed a significant increase in tissue NOx content and an upregulation of iNOS protein abundance in thoracic aorta, heart, and kidney and of nNOS protein expression in the brain and kidney but no discernible change in eNOS expression. This was associated with marked attenuation of hypertensive response to norepinephrine and a significant increase in hypertensive response to aminoguanidine, suggesting enhanced iNOS-derived NO generation in the HU group. Upregulation of these NOS isotypes can contribute to cardiovascular adaptation to microgravity by promoting vasodilatory tone and natriuresis and depressing central sympathetic outflow. If true in humans, short-term administration of an iNOS inhibitor may ameliorate orthostatic intolerance in returning astronauts and patients after extended bed rest.     

Role of individual predisposition in orthostatic intolerance before and after simulated microgravity.

Orthostatic intolerance (OI) is a major problem after spaceflight. Its etiology remains uncertain, but reports have pointed toward an individual susceptibility to OI. We hypothesized that individual predisposition plays an important role in post-bed rest OI. Twenty-four healthy male subjects were equilibrated on a constant diet, after which they underwent tilt-stand test (pre-TST). They then completed 14-16 days of head-down-tilt bed rest, and 14 of the subjects underwent repeat tilt-stand test (post-TST). During various phases, the following were performed: 24-h urine collections and hormonal measurements, plethysmography, and cardiovascular system identification (a noninvasive method to assess autonomic function and separately quantify parasympathetic and sympathetic responsiveness). Development of presyncope or syncope defined OI. During pre-TST, 11 subjects were intolerant and 13 were tolerant. At baseline, intolerant subjects had lower serum aldosterone (P < 0.01), higher excretion of potassium (P = 0.01), lower leg venous compliance (P = 0.03), higher supine parasympathetic responsiveness (P = 0.02), and lower standing sympathetic responsiveness (P = 0.048). Of the 14 subjects who completed post-TST, 9 were intolerant and 5 were tolerant. Intolerant subjects had lower baseline serum cortisol (P = 0.03) and a higher sodium level (P = 0.02) compared with tolerant subjects. Thus several physiological characteristics were associated with increased susceptibility to OI. We propose a new model for OI, whereby individuals with greater leg venous compliance recruit compensatory mechanisms (activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, and withdrawal of the parasympathetic nervous system) in the face of daily postural challenges, which places them at an advantage to face orthostatic stress. With head-down-tilt bed rest, the stimulus to recruit compensatory mechanisms disappears, and differences between the two subgroups attenuate.     

Metabolic adaptation to prolonged exercise.

A study was undertaken to evaluate and to examine the role of substrate supply in 50 healthy subjects after long distance events, such as 10 km, 25 km, and marathon races. The metabolic, variables of carbohydrate metabolism were greatest in 10-km runners, with the highest increase in glucose, lactate, and pyruvate, while in marathon runners only moderate changes were observed. Marathon competitors gave the greatest decrease in insulin concentration whereas glucagon and cortisol showed a contrary tendency. As for lipid concentrations, the most remarkable point was that after the marathon competition the best runners had the highest increase in free fatty acids; the longer the race, the higher were the beta-hydroxybutyrate and acetoacetate levels after the competition. It is important to emphasize that the limiting factor up to 90 min duration is the competitor's ability to deplete the stores of glycogen. Beyond 90 min (or 25 km) the decrease in insulin, the rise in cortisol and the higher concentration of ketnne bodies found indicate a change in metabnlic response.     

Sex differences in left ventricular function and beta-receptor responsiveness following prolonged strenuous exercise.

Sex differences in neuroendocrine and metabolic responses to prolonged strenuous exercise (PSE) have been well documented. The aim of this investigation was to examine sex differences in left ventricular function and cardiac beta-receptor responsiveness following a single bout of PSE. Nine male and eight female triathletes were examined during three separate sessions: before, immediately after, and 24 h following a half-ironman triathlon using dobutamine stress echocardiography. Steady-state graded infusions of dobutamine were used to assess beta-receptor responsiveness. Slopes calculated from linear regressions between dobutamine doses and changes in heart rate and contractility for each participant were used as an index of beta-receptor responsiveness. Despite no change in preload, fractional area change decreased from baseline after the race in both men and women, with a greater decrease in men [men: 54.1% (SD 2.1) to 50.7% (SD 3.4) vs. women: 55.4% (SD 2.7) to 53.3% (SD 2.5); P < 0.05]. The amount of dobutamine necessary to increase heart rate by 25 beats/min [men: 29.6 microg x kg(-1) x min(-1) (SD 6.6) to 42.7 microg x kg(-1) x min(-1) (SD 12.9) vs. women: 23.5 microg x kg(-1) x min(-1) (SD 4.0) to 30.0 microg x kg(-1) x min(-1) (SD 7.8); P < 0.05] and contractility by 10 mmHg/cm2 [men: 20.9 microg x kg(-1) x min(-1) (SD 5.1) to 37.0 microg x kg(-1) x min(-1) (SD 11.5) vs. women: 22.6 microg x kg(-1) x min(-1) (SD 6.4) to 30.7 microg x kg(-1) x min(-1) (SD 7.2); P < 0.05] was greater in both men and women postrace. However, the amount of dobutamine required to induce these changes was greater in men, reflecting larger beta-receptor alterations in male triathletes following PSE relative to women. These data suggest that following an acute bout of PSE, male triathletes demonstrate an attenuated chronotropic and inotropic response to beta-adrenergic stimulation compared with female triathletes.     

Limb venous compliance in patients with idiopathic orthostatic intolerance and postural tachycardia.

Venous denervation and increased venous pooling may contribute to symptoms of orthostatic intolerance. We examined venous compliance in the calf and forearm in 11 orthostatic-intolerant patients and 15 age-matched controls over a range of pressures, during basal conditions and sympathetic excitation. Occlusion cuffs placed around the upper arm and thigh were inflated to 60 mmHg and deflated to 10 mmHg over 1 min. Limb volume was measured continuously with a mercury-in-Silastic strain gauge. Compliance was calculated as the numerical derivative of the pressure-volume curve. The pressure-volume relationship in the upper and lower extremities in the basal and sympathetically activated state was significantly lower in the orthostatic-intolerant patients (all P < 0.05). Sympathoexcitation lowered the pressure-volume relationship in the lower extremity in patients (P < 0.001) and controls (P < 0.01). Venous compliance was significantly less in patients in the lower extremity in the basal state over a range of pressures (P < 0.05). Venous compliance was less in patients compared with controls in the upper (P < 0.005) and lower extremities (P < 0.01) in the sympathetically activated state, but there were no differences at individual pressure levels. Sympathetic activation did not change venous compliance in the upper and lower extremity in patients and controls. Patients with orthostatic intolerance have reduced venous compliance in the lower extremity. Reduced compliance may limit the dynamic response to orthostatic change and thereby contribute to symptoms of orthostatic intolerance in this population group.     

Physical fitness and cardiovascular regulation: mechanisms of orthostatic intolerance

We studied three groups of eight men each--high, mid, and low fit (peak O2 consumption 60.0 +/- 0.8, 48.9 +/- 1.0, and 35.7 +/- 0.9 ml.min-1.kg-1)--to determine the mechanism of orthostatic intolerance in endurance athletes. Tolerance was defined by progressive lower body negative pressure (LBNP) to presyncope. Maximal calf vascular conductance (Gmax) was measured. The carotid baroreflex was characterized using both stepwise R-wave-triggered and sustained (2 min) changes in neck chamber pressure. High-fit subjects tended to have lower LBNP tolerance than mid- and low-fit subjects but similar baroreflex responses. Subjects with poor LBNP tolerance had larger stroke volumes (SV) (120 +/- 6 vs. 103 +/- 3 ml) and greater decline in SV with LBNP to -40 mmHg (40 +/- 2 vs. 26 +/- 4%). Stepwise multiple linear regression analysis revealed that Gmax and steady-state gain of the carotid baroreflex contributed significantly toward explaining interindividual variations in LBNP tolerance. Thus endurance athletes may have decreased LBNP tolerance, but apparently not as a simple linear function of aerobic fitness. Orthostatic tolerance depends on complex interactions among functional characteristics that appear both related (Gmax and SV) and unrelated (baroreflex function) to fitness or exercise training.     

Neuroendocrine changes involved in the genesis of HD-induced orthostatic intolerance

The aim of the present study was to analyze the role played by norepinephrine and epinephrine in Symptomatic (S) vs Non-Symptomatic (NS) subjects within a group of healthy volunteers undergoing a 4-hour-head-down bed rest study at -6 degrees.     

Basal very low-density lipoprotein metabolism in response to exercise: Mechanisms of hypotriacylglycerolemia

Although the hypotriacylglycerolemic effect of exercise was described more than 40 years ago, the mechanisms responsible for triacylglycerol (TAG)-lowering have just recently started to be elucidated. Delayed-onset hypotriacylglycerolemia in the basal state, 1 day after a single bout of endurance exercise is due to augmented efficiency of very low-density lipoprotein (VLDL)-TAG removal from the circulation, likely mediated by the secretion of fewer but TAG-richer VLDL particles from the liver; exercise-induced changes in skeletal muscle lipoprotein lipase are more likely a contributing rather than the primary factor of TAG-lowering. This illustrates, in vivo, how changes in VLDL-apolipoprotein B-100 metabolism in the liver can effect changes in VLDL-TAG metabolism in the periphery. The exercise-induced increase in basal VLDL-TAG clearance rate plateaus at ～40%, whereas the threshold of energy that needs to be expended during endurance exercise lies near or above 500–600 kcal. Resistance exercise is more potent than endurance exercise in this respect. Exercise-induced changes in basal hepatic VLDL-TAG secretion 12–24 h after exercise are not negligible but span around zero; available data indicates that reduced hepatic VLDL-TAG secretion rate may be responsible for the persistence of hypotriacylglycerolemia at later time points (?48 h) after exercise cessation, or following training. Our understanding of the mechanisms leading to TAG-lowering after exercise has advanced considerably in recent years, but much remains to be learned.